Trauma is the major cause of mortality in individuals under 45 years of age and accounts for a large percentage of those killed in military combat, with exsanguination being the principal cause of trauma mortality. Life-threatening hemorrhages occur both in profuse bleeding from solid organs, (for example, AAST-OIS grades IV and V complex hepatic injuries), and from bleeding in regions that are difficult to access (particularly the pelvic area). Through our preliminary work, we have demonstrated the potential of High Intensity Focused Ultrasound (HIFU) to induce vascular and organ hemorrhage hemostasis in animal models. Ultrasound also provides a useful and highly-developed imaging modality that is in widespread use in a clinical environment. We propose to utilize both the imaging and therapeutic capabilities of ultrasound to develop a specific device and a methodology for the intraoperative treatment of profuse bleeding, particularly AAST-OIS grades IV and V complex hepatic injuries, which have a high mortality rate, and for severe wounds in the pelvic area. The current clinical approach to severe hepatic injuries is to pack the wounds until hemodynamic stability is achieved, and then to transfer the patient to the angiography suite where angioembolization of the damaged vessels is performed. Valuable time is lost in this transfer because angiography cannot be performed in the operating room. We have considerable preliminary data in animal models that suggests that an image-guided HIFU device could be used to induce hemostasis at the site of the wound, or to occlude the vessels supplying the bleeding site, immediately, and within the confines of the operating room, thus obviating the need for angioembolization, and/or significant operative maneuvers. Our proposal describes four general tasks that need to be accomplished to meet this exciting goal: (1) To utilize ultrasound contrast agents to improve bleeding detection; (2) To develop ultrasound techniques and protocols for detection, localization, and targeting of bleeding sites; (3) To develop an integrated image guided HIFU therapy system; and (4) To perform in vivo experiments on a porcine model to demonstrate the capabilities of image-guided intraoperative acoustic hemostasis. Finally, progress in this area would provide a firm foundation for the ultimate goal of this research-that of a fully automated, portable, image-guided transcutaneous acoustic hemostasis device that could be used by first responders in civilian trauma injuries. [unreadable] [unreadable] [unreadable]